Fulminant hepatitis in a hepatitis B surface antigen-positive patient with adult T-cell leukemia-lymphoma after mogamulizumab monotherapy.

We report a case of fulminant hepatitis in a hepatitis B surface antigen (HBsAg)-positive patient with aggressive adult T-cell leukemia-lymphoma who received monotherapy with an anti-CCR4 monoclonal antibody, mogamulizumab, with decreased hepatitis B virus (HBV)- DNA levels by entecavir prophylaxis. Although HBV reactivation-related hepatitis was considered in the differential diagnosis, the patient did not meet the conventional criteria for HBV reactivation and was finally diagnosed with drug-induced hepatitis. Considering that the immunoenhancing effects of mogamulizumab can lead to HBV reactivation-related hepatitis in HBsAg-positive patients, we should differentiate drug-induced hepatitis from HBV reactivation, especially in patients receiving immunomodulatory drugs, if HBV-DNA levels are reduced by antiviral prophylaxis.

[A case of R0 resection in conversion surgery after duodenal stent placement for locally advanced unresectable pancreatic cancer with duodenal stenosis].

A 67-year-old man presented to our hospital with vomiting. Esophagogastroduodenoscopy revealed duodenal stenosis and atypical epithelium. A tumor in the pancreatic head, about 30mm in size, involving the superior mesenteric artery and a superior mesenteric vein was identified using abdominal contrast computed tomography (CT). Locally advanced pancreatic cancer was diagnosed in the patient through an endoscopic biopsy. Due to the duodenal stenosis complication, duodenal stent placement was conducted. After stent placement, oral intake was resumed, and improvement of the systemic condition led to chemotherapy (modified FOLFIRINOX). After chemotherapy, CT revealed decreased carcinoma progression and vascular invasion. Conversion surgery was improved, and R0 resection was achieved. Our study showed that duodenal stent placement could enhance prognosis;as a result, it was regarded as a good choice for multidisciplinary therapy.

Clinical Significance of Cytomegalovirus Reactivation in Patients With Plasma Cell Dyscrasia Who Were Treated With Anti-CD38 Monoclonal Antibody: A Retrospective Analysis in a Single Institution.

INTRODUCTION: Anti-CD38 monoclonal antibodies (mAbs) have improved the prognosis of patients with plasma cell dyscrasia (PCD), but are also associated with increased infectious adverse events. Cytomegalovirus (CMV) is a common latent pathogen that is reactivated in immunocompromised individuals. Although CMV reactivation has mostly been reported after high-dose chemotherapy followed by stem cell transplantation in patients with PCD, cases of reactivation during anti-CD38 mAb therapy have been reported recently. Due to limited studies, we aimed to determine the frequency and impact of CMV reactivation during anti-CD38 mAb therapy. PATIENTS AND METHODS: This retrospective analysis included 154 consecutive patients with PCD who were treated with anti-CD38 mAbs at a single institution. RESULTS: Seventy-six patients were evaluated for CMV reactivation by CMV pp65 antigen testing, and 29 (38%) patients, including nine with newly diagnosed PCD, showed positive results. Patients who tested positive for the CMV pp65 antigen had substantially lower serum albumin levels than those who tested negative. However, the two groups showed no marked difference in the concurrent anti-PCD medications or baseline absolute lymphocyte count. Although most patients showing positive results in the CMV pp65 antigen test had mild or no symptoms, with fever being the most common symptom, some patients developed CMV end-organ disease. In addition, CMV reactivation interfered with the course of anti-PCD treatment in most patients, necessitating dose reductions, delays, and discontinuation of chemotherapy. CONCLUSION: This study provides an overview of the clinical impact of CMV reactivation in patients with PCD treated with anti-CD38 mAb-containing regimens.

Real-world data on efficacy/safety and economic impact of nivolumab administered every 2 and 4 weeks among Japanese patients.

AIM: A new treatment interval for nivolumab administration at 480 mg every 4 weeks, in addition to 240 mg every 2 weeks, was approved in Japan in 2020. Using model-based evaluation, it was speculated that the effects or safety of nivolumab do not differ between the two treatment intervals; however, real-world data on nivolumab efficacy, safety, and economic impact are lacking. Accordingly, we aimed to examine the effects of nivolumab treatment intervals (2 weeks vs. 4 weeks) in terms of efficacy, safety, and economic impact in Japanese patients with cancer. METHODS: We retrospectively analyzed 126 patients treated with nivolumab. The patients were divided into two groups depending on whether they received nivolumab at 240 mg every 2 weeks (2-week group) or 480 mg every 4 weeks (4-week group). RESULTS: Efficacy results found no significant difference between the 4- and 2-week groups considering median overall survival (p = 0.70) and median progression-free survival (p = 0.57). The incidence of any grade and ≥  grade 3 immune-related adverse events did not differ between the 4-week and 2-week groups (any grade, p = 0.13; ≥  grade 3, p = 0.36). Excluding drug costs, the 4-week group had significantly lower medical costs than the 2-week group (2-week vs. 4-week: mean, 94,659 JPY [679.0 USD] vs. 58,737 JPY [421.3 USD]; p < 0.05). CONCLUSION: Collectively, our findings suggest that nivolumab 480 mg every 4 weeks may be more effective than nivolumab 240 mg every 2 weeks in terms of economic impact.

Low-dose fluconazole as a useful and safe prophylactic option in patients receiving allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Invasive fungal infections (IFIs) represent a potentially fatal complication in patients who undergo allogeneic hematopoietic stem cell transplantation (HSCT) if the initiation of therapy is delayed. Some guidelines recommend antifungal prophylaxis or preemptive therapy for these patients depending on the risk of IFIs following allogeneic HSCT. This retrospective study aimed to identify the group of patients who safely undergo allogeneic HSCT with low-dose fluconazole (FLCZ) prophylaxis (100 mg/day). METHODS: We retrospectively reviewed 107 patients who underwent their first allogeneic HSCT at Nagoya City University Hospital from January 1, 2010, to December 31, 2019. We analyzed the efficacy of low-dose FLCZ prophylaxis and investigated the relationship between major risk factors and antifungal prophylaxis failure (APF) within 100 days post-transplant. RESULTS: Of the 107 patients, 70 received low-dose FLCZ prophylaxis, showing a cumulative incidence of APF of 37.1% and a proven/probable IFI rate of 4.3%. There were no fungal infection-related deaths, including Aspergillus infections, in the FLCZ prophylaxis group. In a multivariable analysis, cord blood transplantation (CBT) (subdistribution hazard ratio (SHR), 3.55; 95% confidence interval (CI), 1.44-8.77; p = 0.006) and abnormal findings on lung CT before transplantation (SHR, 2.24; 95% CI, 1.02-4.92; p = 0.044) were independent risk factors for APF in the FLCZ prophylaxis group. CONCLUSION: Low-dose FLCZ prophylaxis is a useful and safe option for patients receiving allogeneic HSCT, except in those undergoing CBT or having any fungal risk features including history of fungal infections, positive fungal markers, and abnormal findings on lung CT before transplantation.

Kinetic study of NADPH activation using ubiquinone-rhodol fluorescent probe and an IrIII-complex promoter at the cell interior.

Nicotine adenine dinucleotide derivatives NADH and NADPH are intimately involved in energy and electron transport within cells. The fluorescent ubiquinone-rhodol (Q-Rh) probe is used for NADPH activation monitoring. Q-Rh reacts with NADPH yielding its quenched hydroquinone-rhodol (H2Q-Rh) form with concurrent NADPH activation (i.e. NADP+ formation). NADPH activation can be enhanced by the addition of an IrIII-complex (i.e. [(η5-C5Me5)Ir(phen)(H2O)]2+) as a promoter. The rate of the Q-Rh fluorescence quenching process is proportional to the NADPH activation rate, which can be used to monitor NADPH. Experiments were performed in phosphate-buffered saline (PBS) solution and on HeLa cell cultures to analyze the kinetics of Q-Rh reduction and the influence of the IrIII-complex promoter on the activation of NADPH (in PBS) and of other intracellular reducing agents (in HeLa cells). There is a substantial increase in Q-Rh reduction rate inside HeLa cells especially after the addition of IrIII-complex promoter. This increase is partly due to a leakage process (caused by IrIII-complex-induced downstream processes which result in cell membrane disintegration) but also involves the nonspecific activation of other intracellular reducing agents, including NADH, FADH2, FMNH2 or GSH. In the presence only of Q-Rh, the activation rate of intracellular reducing agents is 2 to 8 times faster in HeLa cells than in PBS solution. When both Q-Rh and IrIII-complex are present, the rate of the IrIII-complex catalyzed reduction reaction is 7 to 23 times more rapid in HeLa cells. Concentration- and time-dependent fluorescence attenuation of Q-Rh with third-order reaction kinetics (reasonably approximated as pseudo-first-order in Q-Rh) has been observed and modelled. This reaction and its kinetics present an example of "bioparallel chemistry", where the activation of a molecule can trigger a unique chemical process. This approach stands in contrast to the conventional concept of "bioorthogonal chemistry", which refers to chemical reactions that occur without disrupting native biological processes.

Eosinophil may be a predictor of immune-related adverse events induced by different immune checkpoint inhibitor types: A retrospective multidisciplinary study.

BACKGROUND: Immune checkpoint inhibitors (ICIs) can cause severe immune-related adverse events (irAEs). However, biomarkers for irAEs common to different types of ICIs and cancers have not been reported. This study examined whether eosinophils can be used as a predictor of irAEs. METHODS: Six hundred fourteen patients with cancer (esophageal, gastric, head and neck, lung, melanoma, renal cell, urothelial, and other cancer) received anti-PD-1, anti-PD-L1, or anti-CTLA-4 plus anti-PD-1 therapy. The patients were divided into two groups depending on whether they experienced irAEs (irAE group) or not (non-irAE group). Eosinophils were examined before the two-course treatment. RESULTS: Patients in the irAE group who received anti-PD-1 or anti-CTLA-4 plus anti-PD-1 therapy had higher eosinophils before the two-course treatment than those in the non-irAE group (p < 0.05). The eosinophils in the anti-PD-L1 therapy group tended to increase in the irAE group. Furthermore, eosinophils in gastric, head and neck, lung, melanoma, renal, and urothelial cancers were significantly higher in the irAE group than in the non-irAE group (p < 0.05). The optimal cutoff value for eosinophils against irAEs was 3.0% (area under the curve = 0.668). In multivariate analyses, eosinophils of ≥3.0% were an independent factor for irAEs (odds ratio: 2.57, 95% CI: 1.79-3.67). CONCLUSION: An increased eosinophil before the two-course treatment may be a predictor of irAEs in various cancers treated with different ICIs.

Prevalence of psychological distress and associated factors among patients undergoing comprehensive genomic profiling testing: protocol for a multicentre, prospective, observational study.

INTRODUCTION: Since May 2019, comprehensive genomic profiling (CGP) has been covered by Japan's health insurance system for patients with solid tumours that have progressed on standard chemotherapy, rare tumours or tumours of unknown primary origin. Although CGP has the potential to identify actionable mutations that can guide the selection of genomically matched therapies for patients with advanced cancer and limited treatment options, less than 10% of patients benefit from CGP testing, which may have a negative impact on patients' mental status. The aim of this study is to investigate the prevalence of psychological distress and associated factors among patients with advanced cancer who are undergoing CGP testing across Japan. METHODS AND ANALYSIS: This multicentre, prospective cohort study will enrol a total of 700 patients with advanced cancer undergoing CGP testing. Participants will be asked to complete questionnaires at three timepoints: at the time of consenting to CGP testing (T1), at the time of receiving the CGP results (T2; 2-3 months after T1) and 4-5 months after T2 (T3). Primary outcome is the prevalence of depression as measured by the Patient Health Questionnaire-9 at the three timepoints. Secondary outcomes are the prevalence of anxiety and Quality of Life Score. Associated factors with psychological distress will also be examined, including knowledge about CGP, attitudes, values and preferences towards CGP, satisfaction with oncologists' communication and patient characteristics as well as medical information including CGP test results and genomically matched therapies if provided. The prevalence of depression and anxiety will be estimated using the unadjusted raw rates observed in the total sample. Longitudinal changes in measures will be explored by calculating differences between the timepoints. Multivariate associations between variables will be examined using multiple or logistic regression analysis depending on the outcomes to adjust for confounders and to identify outcome predictors. ETHICS AND DISSEMINATION: This study was approved by the Institutional Review Board of the National Cancer Center Japan on 5 January 2023 (ID: 2022-228). Study findings will be disseminated through peer-reviewed journals and conference presentations. TRIAL STATUS: The study is currently recruiting participants and the enrolment period will end on 31 March 2025, with an expected follow-up date of 31 March 2026. TRIAL REGISTRATION NUMBER: UMIN000049964.

The Relationship between Changes in Serum Element Concentrations and Pathological Condition and Disease Status in Japanese Multiple Myeloma Patients: A Pilot Study and Literature Review.

BACKGROUND: Multiple myeloma (MM) is a rare cancer, and information on its pathological condition and serum element levels is lacking. In this pilot study, we examined serum element concentrations in Japanese patients with MM by a comprehensive multi-element analysis. METHODS: This is a case-control study of 12 Japanese patients diagnosed with MM at the Nagoya City University Hospital between 2008 and 2013. Blood samples were taken, at the initial diagnosis and at relapse. The serum concentrations of 12 elements were analyzed by inductively coupled plasma mass spectrometry and compared between MM patients and non-MM volunteers. We also analyzed the correlation between serum element concentrations and laboratory values related to disease status and tumor volume of MM. RESULTS: We found that serum chromium (Cr), copper (Cu), molybdenum (Mo), and barium (Ba) concentrations were significantly increased in MM patients. Ba was significantly increased in MM patients, suggesting an association with bone lesions. There was no consistent trend between these elements and existing indices related to MM tumor volume and disease status. CONCLUSIONS: Although this is a pilot study, serum Cr, Cu, Mo, and Ba concentrations were found to be significantly elevated in MM patients. Further studies with large sample sizes are needed, since the changes in serum concentrations of these elements may reflect the pathological condition of MM.

Laryngeal edema as a symptom of local cytokine release syndrome after BCMA-targeting CAR-T therapy for relapsed and refractory multiple myeloma.

Cytokine release syndrome (CRS) can be a major side effect of chimeric antigen receptor T-cell (CAR-T) therapy, and may occasionally become life-threatening in patients with factors such as high tumor burden or poor performance status. Among the many CRS events observed in B-cell maturation antigen (BCMA)-targeting CAR-T therapy, local symptoms (also called local CRS) are poorly understood due to their low frequency. Here, we present the case of a 54-year-old woman with refractory multiple myeloma exhibiting laryngeal edema as a local CRS. Before CAR-T therapy, she was diagnosed with progressive disease indicated by a left thyroid mass. After local irradiation, she received the BCMA-targeting CAR-T agent idecabtagene vicleucel (ide-cel). On day 2, the patient developed CRS, which resolved on treatment with tocilizumab. However, on day 4, laryngeal edema worsened, and was judged to be a local CRS. Intravenous dexamethasone rapidly reduced this edema. In conclusion, laryngeal edema rarely occurs as a local CRS, and to the best of our knowledge, has never been reported after ide-cel infusion. Dexamethasone was effective for reducing the local reaction that persisted after treatment of systemic symptoms with tocilizumab.

Humoral and cellular immune response to second and third severe acute respiratory syndrome coronavirus 2 mRNA vaccine in patients with plasma cell dyscrasia.

BACKGROUND: The recently developed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine has a short history of use and further information is needed regarding its efficacy, especially in immunocompromised conditions, such as plasma cell dyscrasia (PCD). METHODS: We retrospectively measured serum SARS-CoV-2 antibodies against the spike protein (S-IgG) after the second and third mRNA vaccine doses (doses 2 and 3, respectively) in 109 patients with PCD. We evaluated the proportion of patients with an adequate humoral response (defined as S-IgG titers ≥300 antibody units/mL). RESULTS: Although active anti-myeloma treatments prior to vaccination had a significantly negative impact on adequate humoral response, specific drug subclasses including immunomodulatory drugs, proteasome inhibitors, and monoclonal antibodies were not negatively associated, except for B-cell maturation antigen-targeted therapy. Dose 3 (booster vaccination) led to significantly higher S-IgG titers and more patients acquired an adequate humoral response. Furthermore, evaluation of vaccine-induced cellular immune response in patients using T-spot Discovery SARS-CoV-2 kit, revealed an enhanced cellular immune response after Dose 3. CONCLUSIONS: This study highlighted the significance of booster SARS-CoV-2 mRNA vaccination in patients with PCD with respect to humoral and cellular immunity. Moreover, this study highlighted the potential impact of certain drug subclasses on vaccine-induced humoral immune response.

Case report: Genomic analysis of a therapy-related chronic myelomonocytic leukemia with KMT2A rearrangement that progressed to acute myeloid leukemia with acute promyelocytic leukemia-like features.

We report a 69-year-old female who was a human T-cell leukemia virus type 1 carrier and exhibited a unique clinical course of developing three hematological malignancies within a short period: diffuse large B-cell lymphoma (DLBCL), chronic myelomonocytic leukemia (CMMoL), and acute myeloid leukemia (AML). Although the blast cells in AML showed typical morphological and immunophenotypical features of acute promyelocytic leukemia (APL), it did not harbor RARα gene fusion and thus initially diagnosed as APL-like leukemia (APLL). The patient developed heart failure with a fulminant clinical course and died soon after the diagnosis of APLL. Retrospective analysis with whole-genome sequencing detected a chromosomal rearrangement between KMT2A and ACTN4 gene loci both in CMMoL and APLL samples, but not in the DLBCL sample. Therefore, CMMoL and APLL were considered to be derived from the same clone with KMT2A translocation associated with prior immunochemotherapy. However, KMT2A rearrangement is rarely found in CMMoL in general and ACTN4 is also a rare partner of KMT2A translocation. Thus, this case did not follow typical transformational process of CMMoL or KMT2A-rearranged leukemia. Importantly, additional genetic alterations, including NRAS G12 mutation, were found in APLL, but not in CMMoL samples, suggesting that they might contribute to leukemic transformation. This report highlights the diverse effects of KMT2A translocation and NRAS mutation on the transformation of hematological cells as well as the importance of upfront sequencing analysis to detect genetic backgrounds for a better understanding of therapy-related leukemia.

A comprehensive evaluation of humoral immune response to second and third SARS-CoV-2 mRNA vaccination in patients with malignant lymphoma.

More information is needed regarding the efficacy of SARS-CoV-2 mRNA vaccines in immunocompromised populations, including patients with malignant lymphoma. This study aimed to evaluate humoral responses to the second and third mRNA vaccine doses in 165 lymphoma patients by retrospective analysis of serum SARS-CoV-2 spike protein antibody (S-IgG) titers. Patients with S-IgG titers ≥ 300, 10-300, and ≤ 10 binding antibody units (BAU)/mL were defined as adequate responders, low responders, and non-responders, respectively. S-IgG titers > 10 BAU/mL were considered to indicate seroconversion. After the second dose, 56%, 16%, and 28% of patients were adequate responders, low responders and non-responders, respectively. Multivariate analysis revealed that being an adequate responder after the second dose was associated with receiving the vaccine > 12 months after last chemotherapy, total peripheral lymphocyte count of ≥ 1000/µL, estimated glomerular filtration rate of ≥ 50 mL/min/1.73 m2, and vaccine type (mRNA-1273). After the third dose, patients had significantly higher S-IgG titers and a greater proportion achieved seroconversion. With this third dose, 26% of second-dose non-responders achieved seroconversion and 68% of second-dose low responders became adequate responders. Subsequent SARS-CoV-2 mRNA vaccinations may elicit an immune response in immunocompromised patients who do not initially respond to vaccination.

Aberrant tryptophan metabolism leads to unfavorable outcomes in lenalidomide-treated myeloma patients.

Indoleamine 2,3-dioxygenase 1 (IDO), an enzyme that metabolizes tryptophan (Trp) to kynurenine (Kyn), is an important microenvironmental factor suppressing antitumor immunity. Here, we investigated the clinical impact of aberrant Trp metabolism in patients with multiple myeloma (MM) treated with lenalidomide (Len) and evaluated its effects on T cell immunity ex vivo. Kyn and Trp concentrations were quantified in sera from 72 patients with relapsed or refractory MM prior to the initiation of therapy with Len plus dexamethasone (Ld). Associations of the Kyn/Trp ratio with progression-free survival (PFS) and overall survival (OS) were analyzed. The expressions of IDO in tumor and stromal cells were evaluated during co-culture, and the effects of culture medium containing low Trp and high Kyn concentrations on T cells in the presence of Len were investigated. Patients with high serum Kyn/Trp ratios (≥46.0, n = 22) had significantly shorter PFS and OS than those with low ratios (4.9 vs. 12.6 months, and 15.5 vs. 45.7 months, respectively). MM cells promoted IDO expression in stromal cells during co-culture in both a direct contact and an indirect manner. Incubation in medium with a high Kyn/Trp ratio significantly inhibited T cell cytokine production and upregulated the expression of inhibitory immune receptors. These effects were sustained even in the presence of Len. In conclusion, a high serum Kyn/Trp ratio is associated with poor prognosis in patients with MM. We propose that aberrant Trp metabolism reduces anti-tumor immunity and the efficacy of Len therapy.

Recurrent pain attacks during romiplostim treatment in a patient with ITP carrying a heterozygous MEFV mutation.

We report a case of recurrent pain attacks during romiplostim treatment in a woman with immune thrombocytopenia carrying a heterozygous MEFV mutation. Five months after starting treatment with romiplostim for immune thrombocytopenia, she was diagnosed with idiopathic pericarditis. She was switched to eltrombopag, but thrombocytopenia did not improve. Romiplostim was restarted 7 months later, although she then developed recurrent right hypochondrial pain. The pain typically occurred three days after the romiplostim injection and resolved two days later. She had never experienced such recurrent pain before starting romiplostim or after discontinuing it. Genetic analysis showed that she carried a heterozygous R202Q alteration in exon 2 of the MEFV gene. MEFV mutation is known to cause familial Mediterranean fever, which is characterized by symptoms such as recurrent fever, abdominal and chest pain, arthritis, and pericarditis. This case suggests that romiplostim has the potential to trigger recurrent pain/inflammation attacks in individuals with systemic inflammatory abnormalities.

A case of metastatic treatment-emergent small cell/neuroendocrine prostate cancer with BRCA2 mutation diagnosed by liver biopsy.

Introduction: Treatment-emergent small cell/neuroendocrine prostate cancer occurs predominantly in advanced or metastatic castration-resistant prostate cancer that arises when prostate adenocarcinoma is transformed after androgen deprivation therapy. The clinical course for the pathogenesis involved or associated genetic information have not been clearly elucidated. Case presentation: A Japanese male, 63-year-old, underwent a para-aortic lymph biopsy due to sudden severe bilateral leg edema, with a final diagnosis of stage IV prostate adenocarcinoma. He was initially responsive to upfront abiraterone with androgen deprivation therapy; however, relapse occurred in the liver and bone 10 months after initial treatment, with serum neuron-specific enolase elevation and without prostate-specific antigen elevation. Pathological findings of liver tumor revealed treatment-emergent small cell/neuroendocrine prostate cancer. FoundationOne® CDx was used for cancer-related gene profiling of liver tumor specimen; a BRCA2 mutation was identified. Conclusion: Early detection of this transformation and pathological diagnosis can improve patient survival when genetic mutations, including BRCA 1/2.

A novel RARA-SNX15 fusion in PML-RARA-positive acute promyelocytic leukemia with t(11;17;15)(q13;q21.2;q24.1).

Acute promyelocytic leukemia (APL) is characterized by a series of retinoic acid receptor (RAR) fusion genes that lead to the dysregulation of RAR signaling and onset of APL. PML-RARA is the most common fusion generated from t(15;17)(q24;q21). In addition, the reciprocal fusion RARA-PML is present in over 80% of t(15;17) APL cases. The bcr3 types of RARA-PML and RARA-PLZF in particular are reciprocal fusions that contribute to leukemogenesis. Here, we report a variant APL case with t(11;17;15)(q13;q21.2;q24.1). Massive parallel sequencing of patient RNA detected the novel fusion transcripts RARA-SNX15 and SNX15-LINC02255 along with the bcr3 type of PML-RARA. Genetic analysis revealed that RARA-SNX15L is an in-frame fusion due to intron retention caused by RNA mis-splicing. RARA-SNX15L consisted mainly of SNX15 domains, including the Phox-homology domain, which has a critical role in protein-protein interactions among sorting nexins and with other partners. Co-immunoprecipitation analysis revealed that RARA-SNX15L is directly associated with SNX15 and with itself. Further studies are needed to evaluate the biological significance of RARA-SNX15L in APL. In conclusion, this is the first report of APL with a complex chromosomal rearrangement involving SNX15.

Acute Promyelocytic Leukemia in a Patient With Chronic Continuous Type of Crohn's Disease.

Chronic inflammation can induce leukemogenic mutations in hematopoietic stem cells (HSCs). We report a case of acute promyelocytic leukemia (APL) in a patient with chronic continuous type of Crohn's disease. The patient had been diagnosed with Crohn's disease at the age of 28 years and had received conventional treatments with biologics, but not azathioprine. At the age of 51, he was diagnosed with APL with ider(17). Long-term exposure to chronic continuous inflammation from Crohn's disease might be a factor inducing genomic instability in HSCs, which lead to the subsequent development of APL. APL is a rare hematological manifestation that required attention in Crohn's disease patients.

Nationwide survey on family caregiver-perceived experiences of patients with cancer of unknown primary site.

PURPOSE: Cancer of unknown primary site (CUP) is an aggressive disease with poor prognosis. As research on the experiences of CUP patients and their families is scarce, this study aimed to compare the family caregiver-perceived burden of CUP with that of common cancers (lung, colon, and stomach cancers). The association between family caregiver-perceived burden and CUP patients' quality of life (QOL) at end-of-life and family depression, respectively, was also explored. METHODS: This was a pre-planned secondary analysis of nationwide cross-sectional survey data from the bereaved family caregivers of patients with cancer who died at 286 institutions. The major measurements were the eight-item family caregiver-perceived Burden scale (comprising specialist access, uncertainty, and prolonged diagnosis), Good Death Inventory, and Patient Health Questionnaire 9. RESULTS: Of 27,591 survey responses, we analyzed 97 and 717 responses from family caregivers of patients with CUP and common cancer, respectively. The families of CUP patients scored significantly higher on all three burden subscales than those of common cancer patients (effect sizes: specialist access subscale, 0.3; uncertainty subscale, 0.66; and prolonged diagnosis subscale, 0.69; adjusted P < 0.01). Greater family burden was significantly associated with lower patient QOL and higher family depression. Burden was significantly associated with being a spouse, second opinion consultation, and diagnosis period of > 1 month. CONCLUSION: The family caregivers of CUP patients experience poor specialist access, greater uncertainty, and a prolonged diagnosis. They should be cared for from the initial stages to establish access to specialists, obtain an early diagnosis, and reduce uncertainty.

Management of hepatitis B virus (HBV) reactivation in patients with resolved HBV infection based on a highly sensitive HB core-related antigen assay.

AIMS: To prevent hepatitis B virus (HBV) reactivation-related hepatitis, we examined the clinical usefulness of a highly sensitive HB core-related antigen (iTACT-HBcrAg) assay in patients with resolved HBV infection after nucleos(t)ide analog (NA) treatment for HBV reactivation. METHODS: We retrospectively analyzed 27 patients with resolved HBV infection who experienced HBV reactivation (defined as HBV DNA levels of 1.3 log IU/ml or more), and who received systemic chemotherapies for hematological malignancies between 2008 and 2020. iTACT-HBcrAg, HBsAg-HQ, and antibodies against hepatitis B surface antigen (anti-HBs) were measured using samples stored after HBV reactivation. The lower limit of quantification for iTACT-HBcrAg was 2.0 log U/ml. RESULTS: HBV reactivation was diagnosed at a median HBV DNA level of 1.8 log IU/ml, and then all patients received NA treatment. No patient had HBV-related hepatitis with a median maximum HBV DNA level of 2.0 log IU/ml. The positivities of iTACT-HBcrAg and HBsAg-HQ were 96% and 52% after HBV reactivation, respectively. Of 25 patients with detectable iTACT-HBcrAg at the initiation of NA treatment, 17 (68%) achieved iTACT-HBcrAg loss. Median durations from NA treatment to HBV DNA loss and iTACT-HBcrAg loss or the last follow-up were 35 and 175 days, respectively. Recurrence of HBV reactivation after NA cessation was not observed in seven of eight patients who achieved iTACT-HBcrAg loss or seropositive for anti-HBs during follow-up, except for one without anti-HBs after allogeneic transplantation. CONCLUSIONS: iTACT-HBcrAg could be a potential surrogate marker for diagnosing early-stage HBV reactivation as well as safe cessation of NA treatment in patients with resolved HBV infection after HBV reactivation.